Interactions between Crizotinib and Zocor

The simvastatin in Zocor has a major potential interaction with Alcoholism.

The use of most HMG-CoA reductase inhibitors is contraindicated in patients with active liver disease, decompensated cirrhosis, or unexplained persistent elevations of serum transaminases. HMG-CoA reductase inhibitors are extensively metabolized by the liver. Decreased drug metabolism may lead to accumulation and increased risk of toxicity, including biochemical abnormalities of liver function and, rarely, jaundice, hepatitis, cirrhosis, fatty change in the liver, and fulminant hepatic necrosis. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with a history of liver disease and/or heavy alcohol use. A lower initial dosage may be appropriate, and clinical monitoring of liver transaminase levels according to the individual manufacturer product information is recommended. Patients who develop elevated ALT or AST levels during therapy should be monitored until abnormalities resolve. If an increase above 3 times the upper limit of normal persists, consideration should be given to a reduction in dosage or withdrawal of therapy.

Crizotinib has a moderate potential interaction with Arrhythmia.

Crizotinib can cause symptomatic bradycardia. Heart rate and blood pressure should be monitored regularly. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for bradycardia as recommended.

Crizotinib has a moderate potential interaction with Arrhythmia.

The use of crizotinib can cause QTc prolongation. It is recommended to avoid the use of this agent in patients with congenital long QT syndrome. Care should be exercised when using this drug in patients with a history of or predisposition to QTc prolongation. ECGs and electrolytes should be monitored in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for QT/QTc interval prolongation as recommended.

The simvastatin in Zocor has a moderate potential interaction with Central Nervous System Disorders.

Cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) have been observed in patients receiving statins. The reports are usually not serious, and reversible upon statin discontinuation. Caution is recommended when using these agents in patients with cognitive impairment.

The simvastatin in Zocor has a moderate potential interaction with Diabetes Mellitus.

Increases in hemoglobin A1c and fasting serum glucose levels have been reported with the use of certain HMG-CoA reductase inhibitors. Caution should be exercised when using these agents in diabetic patients and close monitoring is recommended.

Crizotinib has a moderate potential interaction with Diverticulitis.

The use of crizotinib can cause gastrointestinal (GI) perforations. This drug should be used with caution in patients at risk for GI perforation (e.g., history of diverticulitis, metastases to the gastrointestinal tract, concomitant use of medicinal products with a recognized risk of gastrointestinal perforation). It is recommended to discontinue treatment in patients who develop GI perforation.

Crizotinib has a moderate potential interaction with Electrolyte Abnormalities.

The use of crizotinib can cause QTc prolongation. It is recommended to avoid the use of this agent in patients with congenital long QT syndrome. Care should be exercised when using this drug in patients with a history of or predisposition to QTc prolongation. ECGs and electrolytes should be monitored in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for QT/QTc interval prolongation as recommended.

Crizotinib has a moderate potential interaction with Gastrointestinal Obstruction.

The use of crizotinib can cause gastrointestinal (GI) perforations. This drug should be used with caution in patients at risk for GI perforation (e.g., history of diverticulitis, metastases to the gastrointestinal tract, concomitant use of medicinal products with a recognized risk of gastrointestinal perforation). It is recommended to discontinue treatment in patients who develop GI perforation.

Crizotinib has a moderate potential interaction with Gastrointestinal Perforation.

The use of crizotinib can cause gastrointestinal (GI) perforations. This drug should be used with caution in patients at risk for GI perforation (e.g., history of diverticulitis, metastases to the gastrointestinal tract, concomitant use of medicinal products with a recognized risk of gastrointestinal perforation). It is recommended to discontinue treatment in patients who develop GI perforation.

Crizotinib has a moderate potential interaction with Heart Failure.

The use of crizotinib can cause QTc prolongation. It is recommended to avoid the use of this agent in patients with congenital long QT syndrome. Care should be exercised when using this drug in patients with a history of or predisposition to QTc prolongation. ECGs and electrolytes should be monitored in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for QT/QTc interval prolongation as recommended.

Crizotinib has a moderate potential interaction with Interstitial Lung Disease.

Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur with crizotinib. Care should be exercised when using this drug in patients with preexisting pulmonary impairment. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. Crizotinib should be permanently discontinued in patients diagnosed with drug-related ILD/pneumonitis if no other potential causes of ILD/pneumonitis have been identified.

The simvastatin in Zocor has a major potential interaction with Liver Disease.

The use of most HMG-CoA reductase inhibitors is contraindicated in patients with active liver disease, decompensated cirrhosis, or unexplained persistent elevations of serum transaminases. HMG-CoA reductase inhibitors are extensively metabolized by the liver. Decreased drug metabolism may lead to accumulation and increased risk of toxicity, including biochemical abnormalities of liver function and, rarely, jaundice, hepatitis, cirrhosis, fatty change in the liver, and fulminant hepatic necrosis. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with a history of liver disease and/or heavy alcohol use. A lower initial dosage may be appropriate, and clinical monitoring of liver transaminase levels according to the individual manufacturer product information is recommended. Patients who develop elevated ALT or AST levels during therapy should be monitored until abnormalities resolve. If an increase above 3 times the upper limit of normal persists, consideration should be given to a reduction in dosage or withdrawal of therapy.

Crizotinib has a moderate potential interaction with Liver Disease.

Crizotinib concentrations increased in patients with preexisting moderate (any AST and total bilirubin greater than 1.5 to 3 times the upper limit of normal [1.5 to 3 x ULN]) or severe (any AST and total bilirubin greater than 3 x ULN) liver dysfunction; a reduced dosage of crizotinib is recommended in these patients. Caution is recommended in patients with moderate or severe liver dysfunction. No dose adjustment is recommended in patients with preexisting mild liver dysfunction (AST greater than ULN and total bilirubin up to 1 x ULN or any AST and total bilirubin greater than 1 to 1.5 x ULN).

Cases of drug-induced hepatotoxicity with fatal outcomes have been reported with the use of crizotinib. It is recommended to monitor liver function tests (including ALT, AST, total bilirubin) every 2 weeks during the first 2 months of therapy, then once a month, and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop increased transaminases. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for hepatotoxicity as recommended.

The simvastatin in Zocor has a moderate potential interaction with Myoneural Disorder.

HMG-CoA reductase inhibitors may cause myopathy and rhabdomyolysis; acute renal failure secondary to myoglobinuria and rare fatalities have occurred due to rhabdomyolysis in patients treated with statins. The myopathy may be dose-related and is characterized by unexplained muscle weakness, pain, or tenderness accompanied by increases in creatine phosphokinase (CPK) values exceeding 10 times the upper limit of normal. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with preexisting myopathy, in those with predisposing factors for myopathy, or with a history of myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Periodic CPK determinations may be considered in some patients, although the value of such monitoring is uncertain. HMG-CoA reductase inhibitor therapy should be withdrawn if markedly elevated CPK levels occur or if drug-related myopathy is diagnosed or suspected.

The simvastatin in Zocor has a moderate potential interaction with Myopathy.

HMG-CoA reductase inhibitors may cause myopathy and rhabdomyolysis; acute renal failure secondary to myoglobinuria and rare fatalities have occurred due to rhabdomyolysis in patients treated with statins. The myopathy may be dose-related and is characterized by unexplained muscle weakness, pain, or tenderness accompanied by increases in creatine phosphokinase (CPK) values exceeding 10 times the upper limit of normal. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with preexisting myopathy, in those with predisposing factors for myopathy, or with a history of myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Periodic CPK determinations may be considered in some patients, although the value of such monitoring is uncertain. HMG-CoA reductase inhibitor therapy should be withdrawn if markedly elevated CPK levels occur or if drug-related myopathy is diagnosed or suspected.

Crizotinib has a moderate potential interaction with Pulmonary Impairment.

Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur with crizotinib. Care should be exercised when using this drug in patients with preexisting pulmonary impairment. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. Crizotinib should be permanently discontinued in patients diagnosed with drug-related ILD/pneumonitis if no other potential causes of ILD/pneumonitis have been identified.

The simvastatin in Zocor has a major potential interaction with Renal Dysfunction.

Although simvastatin itself is not eliminated by the kidney, the plasma concentrations of total HMG-CoA reductase inhibitors after a single dose of simvastatin may be increased in patients with significant renal impairment, presumably due to the accumulation of active metabolites. Increased HMG-CoA reductase inhibitory activity may be associated with a greater risk of adverse effects, including hepatic and musculoskeletal toxicities. Therapy with simvastatin should be administered cautiously at a reduced dosage in patients with severe renal impairment. Close clinical monitoring is recommended.

Crizotinib has a moderate potential interaction with Renal Dysfunction.

The exposure to crizotinib is increased in patients with preexisting severe renal dysfunction (CrCl less than 30 mL/min [calculated using the modified Cockcroft-Gault equation for adult patients and the Schwartz equation for pediatric patients]) not requiring dialysis; a reduced dosage of crizotinib is recommended in these patients. Care should be exercised when using this drug in patients with severe renal dysfunction not requiring dialysis. No dose adjustment is recommended in patients with mild to moderate renal dysfunction (CrCl 30 to 89 mL/min).

The simvastatin in Zocor has a moderate potential interaction with Renal Dysfunction.

Some HMG-CoA reductase inhibitors (e.g., fluvastatin) have not been studied in patients with severe renal dysfunction or end-stage renal disease. Some others (e.g., pitavastatin, simvastatin) require a dose reduction when used in this group of patients. Caution and close monitoring are advised when using these drugs in patients with renal dysfunction.

The simvastatin in Zocor has a moderate potential interaction with Renal Dysfunction.

HMG-CoA reductase inhibitors may cause myopathy and rhabdomyolysis; acute renal failure secondary to myoglobinuria and rare fatalities have occurred due to rhabdomyolysis in patients treated with statins. The myopathy may be dose-related and is characterized by unexplained muscle weakness, pain, or tenderness accompanied by increases in creatine phosphokinase (CPK) values exceeding 10 times the upper limit of normal. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with preexisting myopathy, in those with predisposing factors for myopathy, or with a history of myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Periodic CPK determinations may be considered in some patients, although the value of such monitoring is uncertain. HMG-CoA reductase inhibitor therapy should be withdrawn if markedly elevated CPK levels occur or if drug-related myopathy is diagnosed or suspected.

The simvastatin in Zocor has a moderate potential interaction with Underactive Thyroid.

HMG-CoA reductase inhibitors may cause myopathy and rhabdomyolysis; acute renal failure secondary to myoglobinuria and rare fatalities have occurred due to rhabdomyolysis in patients treated with statins. The myopathy may be dose-related and is characterized by unexplained muscle weakness, pain, or tenderness accompanied by increases in creatine phosphokinase (CPK) values exceeding 10 times the upper limit of normal. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with preexisting myopathy, in those with predisposing factors for myopathy, or with a history of myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Periodic CPK determinations may be considered in some patients, although the value of such monitoring is uncertain. HMG-CoA reductase inhibitor therapy should be withdrawn if markedly elevated CPK levels occur or if drug-related myopathy is diagnosed or suspected.

Crizotinib has a moderate potential interaction with Visual Defect/Disturbance.

Cases of optic atrophy and optic nerve disorder leading to vision loss have been reported with the use of crizotinib. Assessment of visual symptoms for all patients is recommended monthly during therapy; new visual symptoms should be reported to an eye specialist. For pediatric and young adult patients with anaplastic large cell lymphoma or inflammatory myofibroblastic tumor, baseline and follow-up ophthalmologic examinations (including retinal examination) should be obtained within 1 month of starting crizotinib and every 3 months thereafter. The ophthalmological evaluation should consist of best corrected visual acuity, retinal photographs, visual fields, optical coherence tomography (OCT), and other evaluations as appropriate. Crizotinib should be permanently discontinued for grade 3 or 4 ocular disorders or severe visual loss (best corrected vision less than 20/200 in 1 or both eyes) unless another cause is identified. There is insufficient information to characterize the risks of resumption of crizotinib in patients who develop visual symptoms or visual loss; a decision to resume treatment with crizotinib should consider the potential benefits versus risks to the patient.